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Einsteins general theory of relativity from 19151 remains the most successful description of gravitation. From the 1919 solar eclipse2 to the observation of gravitational waves3, the theory has passed many crucial experimental tests. However, the evolving concepts of dark matter and dark energy illustrate that there is much to be learned about the gravitating content of the universe. Singularities in the general theory of relativity and the lack of a quantum theory of gravity suggest that our picture is incomplete. It is thus prudent to explore gravity in exotic physical systems. Antimatter was unknown to Einstein in 1915. Diracs theory4 appeared in 1928; the positron was observed5 in 1932. There has since been much speculation about gravity and antimatter. The theoretical consensus is that any laboratory mass must be attracted6 by the Earth, although some authors have considered the cosmological consequences if antimatter should be repelled by matter7-10. In the general theory of relativity, the weak equivalence principle (WEP) requires that all masses react identically to gravity, independent of their internal structure. Here we show that antihydrogen atoms, released from magnetic confinement in the ALPHA-g apparatus, behave in a way consistent with gravitational attraction to the Earth. Repulsive antigravity is ruled out in this case. This experiment paves the way for precision studies of the magnitude of the gravitational acceleration between anti-atoms and the Earth to test the WEP.

Masaki Tago,1 Risa Hirata,1 Naoko E Katsuki,1 Eiji Nakatani,2 Midori Tokushima,1 Tomoyo Nishi,1 Hitomi Shimada,3 Shizuka Yaita,1 Chihiro Saito,4 Kaori Amari,5 Kazuya Kurogi,6 Yoshimasa Oda,7 Kiyoshi Shikino,8,9 Maiko Ono,10 Mariko Yoshimura,11 Shun Yamashita,1 Yoshinori Tokushima,1 Hidetoshi Aihara,1 Motoshi Fujiwara,1 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan; 3Shimada Hospital of Medical Corporation Chouseikai, Saga, Japan; 4Shizuoka General Hospital, Shizuoka, Japan; 5Department of Emergency Medicine, Saga-Ken Medical Centre Koseikan, Saga, Japan; 6Department of General Medicine, National Hospital Organization Ureshino Medical Center, Saga, Japan; 7Department of General Medicine, Yuai-Kai Foundation and Oda Hospital, Saga, Japan; 8Department of General Medicine, Chiba University Hospital, Chiba, Japan; 9Department of Community-Oriented Medical Education, Chiba University Graduate School of Medicine, Chiba, Japan; 10Department of General Medicine, Karatsu Municipal Hospital, Saga, Japan; 11Safety Management Section, Saga University Hospital, Saga, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpPurpose: We conducted a pilot study in an acute care hospital and developed the Saga Fall Risk Model 2 (SFRM2), a fall prediction model comprising eight items: Bedriddenness rank, age, sex, emergency admission, admission to the neurosurgery department, history of falls, independence of eating, and use of hypnotics. The external validation results from the two hospitals showed that the area under the curve (AUC) of SFRM2 may be lower in other facilities. This study aimed to validate the accuracy of SFRM2 using data from eight hospitals, including chronic care hospitals, and adjust the coefficients to improve the accuracy of SFRM2 and validate it.Patients and Methods: This study included all patients aged ≥ 20 years admitted to eight hospitals, including chronic care, acute care, and tertiary hospitals, from April 1, 2018, to March 31, 2021. In-hospital falls were used as the outcome, and the AUC and shrinkage coefficient of SFRM2 were calculated. Additionally, SFRM2.1, which was modified from the coefficients of SFRM2 using logistic regression with the eight items comprising SFRM2, was developed using two-thirds of the data randomly selected from the entire population, and its accuracy was validated using the remaining one-third portion of the data.Results: Of the 124,521 inpatients analyzed, 2,986 (2.4%) experienced falls during hospitalization. The median age of all inpatients was 71 years, and 53.2% were men. The AUC of SFRM2 was 0.687 (95% confidence interval [CI]:0.678– 0.697), and the shrinkage coefficient was 0.996. SFRM2.1 was created using 81,790 patients, and its accuracy was validated using the remaining 42,731 patients. The AUC of SFRM2.1 was 0.745 (95% CI: 0.731– 0.758).Conclusion: SFRM2 showed good accuracy in predicting falls even on validating in diverse populations with significantly different backgrounds. Furthermore, the accuracy can be improved by adjusting the coefficients while keeping the model’s parameters fixed.Keywords: accidental falls, inpatients, validation study, accident prevention

Survival probability is of interest primarily as a component of population dynamics. Only when survival estimates are included in a demographic model are their population implications apparent. Survival describes the transition between living and dead. Biologically important as this transition is, it is only one of many transitions in the life cycle. Others include transitions between immature and mature, unmated and mated, breeding and non¿breeding, larva and adult, small and large, and location x and location y. The demographic consequences of these transitions can be captured by matrix population models, and such models provide a natural link connecting multi-stage mark-recapture methods and population dynamics. This paper explores some of those connections, with examples taken from an ongoing analysis of the endangered North Atlantic right whale (Eubalaena glacialis). Formulating problems in terms of a matrix population model provides an easy way to compute the likelihood of capture histories. It extends the list of demographic parameters for which maximum likelihood estimates can be obtained to include population growth rate, the sensitivity and elasticity of population growth rate, the net reproductive rate, generation time, measures of transient dynamics. In the future, multi-stage mark-recapture methods, linked to matrix population models, will become an increasingly important part of demography.

Dai Shimizu,1 Chie Tanaka,1 Mitsuro Kanda,1 Koki Nakanishi,1 Seiji Ito,2 Yachiyo Kuwatsuka,3 Masahiko Ando,3 Kenta Murotani,4 Michitaka Fujiwara,5 Yasuhiro Kodera1 1Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan; 2Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan; 3Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; 4Biostatistics Center, Graduate School of Medicine, Kurume University, Kurume, Japan; 5Department of Medical Equipment and Supplies Management, Nagoya University Hospital, Nagoya, JapanCorrespondence: Dai Shimizu, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan, Tel +81-52-744-2249, Fax +81-52-744-2255, Email d-shimizu@med.nagoya-u.ac.jpAbstract: Pancreatic fistula after gastrectomy with lymph node dissection is associated with prolonged hospital stay and critical complications such as intra-abdominal bleeding and sepsis. Polyglycolic acid (PGA) sheets are absorbable suture reinforcement materials. A randomized Phase II trial has been planned to evaluate the effect of PGA sheets on preventing postoperative pancreatic fistula. A total of 320 patients will be recruited from thirteen institutions. Patients who are scheduled to undergo distal or total gastrectomy will be randomly allocated into the PGA group or control group, and the dissected area around the pancreas will be covered by the PGA sheet in the PGA group. The primary endpoint will be the maximum value of drain amylase concentration up to 5 days after surgery. The secondary endpoints will be as follows: transition of value of amylases of drain discharge, incidence of pancreatic fistula, incidence of intra-abdominal abscess, white blood cell count, value of C-reactive protein, incidence of postoperative complication, duration of antibiotic agents administration, duration of abdominal drainage, usage of octreotide, duration of hospital stay, incidence of bleeding in abdominal cavity, mortality, and incidence of reoperation.Keywords: gastric cancer, pancreatic fistula, polyglycolic acid sheet, protocol, randomized clinical trial

Akihiko Tanaka,1 Mai Takahashi,2 Ayako Fukui,3 Yoshifumi Arita,3 Masakazu Fujiwara,3 Naoyuki Makita,3 Naoki Tashiro3 1Division of Respiratory Medicine and Allergology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan; 2Medical, AstraZeneca K.K., Tokyo, Japan; 3Medical, AstraZeneca K.K., Osaka, JapanCorrespondence: Akihiko Tanaka, Division of Respiratory Medicine and Allergology, Department of Medicine, School of Medicine, Showa University, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, 142-8666, Japan, Tel +81 3-3784-8000, Fax +81 3-3784-8517, Email tanakaa@med.showa-u.ac.jpPurpose: The oral corticosteroid (OCS)-sparing effect of several biologics (BIOs) has been shown in clinical trials. To date, no study has evaluated differences in OCS dose reduction between BIO-initiated and BIO-non-initiated patients in real-world clinical practice. We compared dose reductions in maintenance OCS between BIO-initiated and BIO-non-initiated severe asthma patients in a real-world setting.Patients and Methods: This retrospective cohort study used the data from the Diagnosis Procedure Combination database of Medical Data Vision in Japan. Severe asthma patients with continuous use of OCS were selected from December 2015 to February 2020. The primary endpoint was the proportion reduction in daily maintenance OCS dose from Week 0 to Week 24. Analyses were performed using inverse probability treatment weighting.Results: In total, 2927 patients were included (BIO-initiated: 239 patients, BIO-non-initiated: 2688 patients). Adjusted median (quartile [Q] 1–Q3) proportion reduction in daily maintenance OCS dose at Week 24 from the index date was 25.0% (0.0– 100.0%) and 0.0% (0.0– 83.3%) in the BIO-initiated and BIO-non-initiated groups, respectively (Hodges–Lehmann estimate [95% confidence interval], 0.0000% [0.0000– 0.3365%]). Respective proportions of patients in the BIO-initiated and BIO-non-initiated groups achieving dose reductions from the index date in the daily maintenance OCS dose at Week 24 were > 0% reduction, 56.6% and 44.1% (odds ratio [OR] 1.6554); ≥ 25% reduction, 50.5% and 40.6% (OR 1.4888); ≥ 50% reduction, 42.8% and 33.7% (OR 1.4714); and 100% reduction, 26.2% and 24.4% (OR 1.1005).Conclusion: Among severe asthma patients, the daily dose of maintenance OCS was reduced with BIO treatment. Although a higher percentage of patients in the BIO-initiated group had an OCS reduction of ≤ 75% than the BIO-non-initiated group, we found no clear difference in OCS reduction. Our findings will be justified by further research that incorporates a longer observation period and variables excluded from this study.Trial Registration: ClinicalTrials.gov (NCT05136547).Keywords: severe asthma, asthma exacerbation, oral corticosteroid, biologics, retrospective cohort study

Yoshinori Tokushima,1,2 Masaki Tago,1,2 Midori Tokushima,1,3 Shun Yamashita,1 Yuka Hirakawa,1 Hidetoshi Aihara,1 Naoko E Katsuki,1 Motoshi Fujiwara,1 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Community Medical Support Institute, Faculty of Medicine, Saga University, Saga, Japan; 3Saga Medical Career Support Center, Saga University Hospital, Saga, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpIntroduction: The educational effects of a hands-on clinical clerkship on medical students at the Department of General medicine of Japanese university hospitals remain to be clarified. This study aimed to determine how such education affects medical students’ self-evaluation of their clinical skills.Methods: We enrolled 5th-year-grade students at the Department of General Medicine, Saga University Hospital, Japan in 2017. The students were divided into those who were going to have Japanese traditional-style observation-based training mainly in the outpatient clinic (Group O) and those in the 2018, new-style, hands-on clinical clerkship as one of the group practice members in outpatient and inpatient clinics (Group H). A questionnaire survey using the 4-point Likert scale for self-evaluation of the students’ clinical skills at the beginning and the end of their training was conducted in both groups. The pre- and post-training scores of each item in both groups were compared and analyzed using the Mann–Whitney test.Results: All 99 students in Group O and 121 of 123 students in Group H answered the questionnaires. The response rate was 99%. Two items regarding the abilities of “can perform a systemic physical examination quickly and efficiently” and “can clearly explain the current medical condition, therapeutic options, or risks associated with treatment, and discuss the process for obtaining informed consent” showed higher scores in the post-training survey in Group H than in Group O. There were no differences in these scores in the pre-training survey between the two groups.Conclusion: A hands-on clinical clerkship at the Department of General medicine in a university hospital in Japan provided medical students with higher self-confidence in their skills of performing a physical examination and better understanding of patients’ treatment options and the process of informed consent than observation-based training.Keywords: general medicine, hands-on clinical clerkship, medical education, observation-based training

Risa Hirata,1 Masaki Tago,1 Naoko E Katsuki,1 Yoshimasa Oda,2 Midori Tokushima,1 Yoshinori Tokushima,1 Yuka Hirakawa,1 Shun Yamashita,1 Hidetoshi Aihara,1 Motoshi Fujiwara,1 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Yuai-Kai Foundation and Oda Hospital, Saga, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81-952-34-3238, Fax +81-952-34-2029, Email tagomas@cc.saga-u.ac.jpIntroduction: In our former study, we had validated the previously developed predictive model for in-hospital falls (Saga fall risk model) using eight simple factors (age, sex, emergency admission, department of admission, use of hypnotic medications, history of falls, independence of eating, and Bedriddenness ranks [BRs]), proving its high reliability. We found that only admission to the neurosurgery department, history of falls, and BRs had significant relationships with falls. In the present study, we aimed to clarify whether each of these three items had a significant relationship with falls in a different group of patients.Methods: This was a single-center based, retrospective study in an acute care hospital in a rural city of Japan. We enrolled all inpatients aged 20 years or older admitted from April 2015 to March 2018. We randomly selected patients to fulfill the required sample size. We performed multivariable logistic regression analysis using forced entry on the association between falls and each of the eight items in the Saga fall risk model 2.Results: A total of 2932 patients were randomly selected, of whom 95 (3.2%) fell. The median age was 79 years, and 49.9% were men. Multivariable analysis showed that female sex (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.39– 0.93, p = 0.022), having a history of falls (OR 1.9, 95% CI 1.16– 2.99, p = 0.010), requiring help with eating (OR 1.9, 95% CI 1.12– 3.35, p = 0.019), BR of A (OR 6.6, 95% CI 2.82– 15.30, p < 0.001), BR of B (OR 7.5, 95% CI 2.95– 19.06, p < 0.001), and BR of C (OR 4.1, 95% CI 1.53– 11.04, p = 0.005) were significantly associated with falls.Conclusion: History of falls and BRs were independently associated with in-hospital falls.Keywords: bedridden, Bedriddenness ranks, fall, predictive model, validation, Saga fall risk model 2

Dark matter (DM) simplified models are by now commonly used by the ATLAS and CMS Collaborations to interpret searches for missing transverse energy (ETmiss). The coherent use of these models sharpened the LHC DM search program, especially in the presentation of its results and their comparison to DM direct-detection (DD) and indirect-detection (ID) experiments. However, the community has been aware of the limitations of the DM simplified models, in particular the lack of theoretical consistency of some of them and their restricted phenomenology leading to the relevance of only a small subset of ETmiss signatures. This document from the LHC Dark Matter Working Group identifies an example of a next-generation DM model, called 2HDM+a, that provides the simplest theoretically consistent extension of the DM pseudoscalar simplified model. A comprehensive study of the phenomenology of the 2HDM+a model is presented, including a discussion of the rich and intricate pattern of mono-X signatures and the relevance of other DM as well as non-DM experiments. Based on our discussions, a set of recommended scans are proposed to explore the parameter space of the 2HDM+a model through LHC searches. The exclusion limits obtained from the proposed scans can be consistently compared to the constraints on the 2HDM+a model that derive from DD, ID and the DM relic density.

Matrix population models (MPMs) are powerful tools for translating demographic and life history information into a form that can be used to address a wide range of research topics, such as projecting population dynamics, evaluating stressor impacts on populations, and studying life history evolution. However, the reliability of such studies depends on the MPM being constructed in a way that accurately reflects the species’ life history. We highlight three errors commonly encountered in published MPMs: (1) failing to include survival in the fertility coefficient; (2) introducing a one-year delay in age at first reproduction; and (3) incorrectly calculating the growth rate out of a stage class. We review the sources of such errors and provide new analyses revealing the impact of such errors on model predictions, using lionfish and American alligator models as examples. To quantify the prevalence of such errors we examined and scored the original publications underlying the models in the COMADRE Animal Matrix Database. The first two errors were found in 34% and 62%, respectively, of the published studies; nearly all were in models that used a “postbreeding census” representation of the life cycle (in which newborns—eggs, neonates, fledglings, etc.—are explicitly included). Of the studies where stages may last longer than one time step, 53% constructed the growth rate using inappropriate formulas for estimating the asymptotic population growth rate or its sensitivity to demographic parameters. These results suggest that further efforts may be required to educate biologists on the construction of MPMs, perhaps in concert with the development of new software tools. Furthermore, the conclusions of many studies that are based on MPMs may need to be re-examined, and synthetic studies using the COMADRE Database need to be accompanied by careful examination of the underlying studies.

Masaki Tago,1 Kiyoshi Shikino,2 Risa Hirata,1 Takashi Watari,3 Shun Yamashita,1 Yoshinori Tokushima,1 Midori Tokushima,1 Hidetoshi Aihara,1 Naoko E Katsuki,1 Motoshi Fujiwara,1 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Chiba University Hospital, Chiba, Japan; 3General Medicine Center, Shimane University Hospital, Shimane, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Email tagomas@cc.saga-u.ac.jpBackground: It is unclear how much effort Japanese university general medicine (GM) departments, which teach basic medical skills and have a high affinity for clinical practice, devote to medical education, particularly undergraduate education. This study aimed to clarify the contribution of GM departments of Japanese universities to medical education.Patients and Methods: This was a questionnaire-based descriptive study of GM departments of Japanese universities. We sent the questionnaire created using Google Forms by email, and the universities responded by Internet. The department chairperson of the universities’ main hospital was responsible for completing the questionnaire. It covered the number of staff, inpatients over the previous 3 years, affiliated hospitals, classroom lectures, and practical training sessions per year for each academic year in medical faculty and students accepted for clinical clerkship. Items also included the effort for clinical training, research, and education and the effort for undergraduate, initial clinical residency, and specialty program training.Results: In all, 46 of 71 universities responded, and we included 43 in our analysis. The median number of medical staff was 7; the median number of inpatients over the previous 3 years was 76. The median number of classroom lectures of the GM department was 1 for 1st-year, 5 for 3rd-year, 9 for 4th-year, and 0 for 2nd-, 5th-, and 6th-year students. The median total number of accepted students for clinical clerkship was 120. The median educational effort of the GM department was 30. With total educational effort set at 100, the median effort for undergraduate education was 45, for postgraduate residency 30, and for specialty program training 20.Conclusion: The undergraduate medical education by GM departments of Japanese universities was provided mainly in clinical settings for almost all medical students. A focus on exposing students to GM in early academic years would improve the educational environment.Keywords: clinical clerkship, general medicine, medical education, specialty program, university

Control of the charge state of the nitrogen-vacancy (NV) center is crucial because of its instability and its transitions between the negative (NV–) and neutral (NV0) NV charge states under laser irradiation In this study, we fabricated an n-i-n junction, with an i-layer sandwiched between two phosphorus-doped n-layers; then, we measured the charge state of NV centers under steady state and laser irradiation in a known band structure where the Fermi energy changes gradually. The steady-state charge state measured by a nondestructive single shot exhibited stable NV– and NV0 signals when the Fermi level was even slightly above and below the transition level, respectively. This result indicates that the charge state can be significantly stabilized through band engineering. Both charge-state populations were observed only when the Fermi level was close to the transition level. Under continuous green laser irradiation, the ratio of NV– measured by the photoluminescence spectra changed gradually with the Fermi level in the depletion layer because of the balance between excitation from the laser and the supply of charge from the band. This outcome agrees reasonably with the calculated bands. Furthermore, we measured the PL spectra of the ensemble NV centers and discovered that their charge state can be well-controlled, as in the single NV center. The charge state of the i-layer at the interface can be stabilized by depositing a thin n-layer on the surface. These results would contribute significantly to improve sensor performance. [ABSTRACT FROM AUTHOR]

Chika Sakai,1 Toshinaga Tsuji,1 Toru Nakai,1 Yuki Namba,1 Hirokazu Mishima,1 Masakazu Fujiwara,2 Hisato Matsunaga3 1Medical Affairs Department, Shionogi & Co. Ltd, Osaka, Japan; 2Data Science Office, Shionogi & Co. Ltd, Osaka, Japan; 3Department of Neuropsychiatry, Hyogo College of Medicine, Hyogo, JapanCorrespondence: Toshinaga TsujiMedical Affairs Department, Shionogi & Co. Ltd, 3-1-8, Doshomachi, Chuo-ku, Osaka-shi, Osaka, 541-0045, JapanTel +81 6 6209 7412Fax +81 6 6202 2239Email toshinaga.tsuji@shionogi.co.jpPurpose: To better understand the treatment of comorbid depression in adults with attention-deficit/hyperactivity disorder (ADHD) by investigating the prescription patterns of antidepressants, anxiolytics, and hypnotics after commencing ADHD medication.Patients and Methods: In this retrospective observational study in Japan, the data of patients initiating ADHD medication while already receiving antidepressants (ADHD group) and of patients prescribed antidepressants but not diagnosed with ADHD (control group) were extracted from an electronic medical record database. Additionally, one-to-one matching for patients in both groups was performed using sex, age, baseline dosage of antidepressants, and any comorbid psychiatric disorders as covariates. The observation period included a 1-month baseline period and a 6-month follow-up period. The percentage of patients prescribed antidepressants and the mean prescribed dosages were compared between matched-cohort groups. Prescriptions for anxiolytics and hypnotics were also assessed.Results: In the matched cohorts, consisting of 239 patients in the ADHD group and 239 patients from the unmatched control cohort of 10,485, the percentage of patients prescribed antidepressants decreased from baseline in both groups to 94.1% in the ADHD group and 89.5% in the control group during the first month of follow-up, and 77.0% and 78.7%, respectively, during the last month. There were no significant differences between groups in the percentages of patients prescribed antidepressants or in the mean prescribed dosages of antidepressants at any time point over the follow-up period. Prescribed dosages of anxiolytics and hypnotics tended to be lower in the ADHD group.Conclusion: The two groups were medicated similarly with respect to their depressive symptoms over 6 months. Our results suggest that in patients with ADHD and comorbid depression, which is more likely to be more severe than in depression without ADHD, depressive symptoms are managed following initiation of add-on ADHD medication, without requiring higher antidepressant dosages than in patients with depression only.Keywords: attention-deficit/hyperactivity disorder, MDD, antidepressants, anxiolytics, hypnotics

Takashi Watari,1,2,* Masaki Tago,3,* Kiyoshi Shikino,4 Shun Yamashita,3 Naoko E Katsuki,3 Motoshi Fujiwara,3 Shu-ichi Yamashita3 1General Medicine Center, Shimane University Hospital, Shimane, Japan; 2Master of Healthcare Quality and Patient Safety, Harvard Medical School, Boston, MA, USA; 3Department of General Medicine, Saga University Hospital, Saga, Japan; 4Department of General Medicine, Chiba University Hospital, Chiba, Japan*These authors contributed equally to this workCorrespondence: Masaki TagoDepartment of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, JapanTel +81 952 34 3238Fax +81 952 34 2029Email tagomas@cc.saga-u.ac.jpPurpose: The training of generalist physicians in university hospitals needs to emphasize development of their research role in order to continue improving their research capacity and their standing in academic hospitals in Japan. This cross-sectional descriptive study aimed to survey departments of general medicine (GM) in university hospitals in Japan to identify the research areas and themes pursued by academic generalist physicians.Patients and Methods: The heads of the departments of GM from 71 university hospitals in Japan were enrolled. The main outcomes studied were the identification of the main research areas and themes in academic departments of GM, based on the classification of the National Grants-in-Aid for Scientific Research (KAKENHI): clinical research, public health, preventive medicine, medical education, basic science, health services and safety and quality.Results: We received 47 of 71 replies (66.2% response rate). Clinical research was the most common area of research (62%), followed by public health and preventive medicine (14%), medical education (11%), and basic sciences (9%). Only one department identified health services and safety and quality as a research area (2%). There was marked variability in research areas across the different departments, with 23% of the research targeting the highest specialties, particularly organ-specific research in the fields of gastroenterology, cardiology, immunology, neurology, metabolic endocrinology, and hematology-oncology.Conclusion: The training of generalist physicians in university hospitals needs to emphasize development of their research role in order to continue improving the research capacity and the standing generalist physicians in academic hospitals in Japan.Keywords: general medicine, research, academic activity

Quantum sensors based on nitrogen-vacancy (NV) centers in diamond are expected to demonstrate a wide variety of applications. For high-sensitivity quantum sensors with NV center ensembles, uniform manipulation of the electron spins of the NV centers in large volumes is required. In addition, a broad microwave frequency bandwidth for manipulating the NV centers' electron spin is necessary for vector magnetometry and measurement under a finite static magnetic field. Here, we demonstrate a broadband microwave antenna for uniform manipulation of millimeter-scale volumes of diamond quantum sensors. The simulation shows that the current is distributed at both edges of the loop coil of a single copper plate due to the skin effect. The loop coil acts like a Helmholtz coil, which realizes uniformity in the z-direction of the microwave magnetic field (B1). The plate structure has a higher mechanical stability, durability, and a larger heat capacity than the Helmholtz coil, due to its large volume. The antenna achieves a higher performance than previously reported antennae, with a maximal B1 of 4.5 G, a broad bandwidth of 287 ± 6 MHz, and a peak-to-peak variation of 9.2 % over a 3.1 mm3 cylinder volume. These performances show that the presented antenna is suitable for manipulating solid-state spin ensembles for high-sensitivity quantum sensors. [ABSTRACT FROM AUTHOR]

Neural crest cells (NCC) arise from the dorsal margin of the neural plate border and comprise a unique cell population that migrates to and creates the craniofacial region. Although factors including Shh, Fgf8, and bone morphogenetic proteins have been shown to regulate these biological events, the role of parathyroid hormone 1 receptor (Pth1r) has been less studied. We generated an NCC-specific mouse model for Pth1r and researched gene expression, function, and interaction focusing on nasal cartilage framework and midfacial development. Wnt1-Cre;Pth1r fl / fl ; Tomato fl /+ mice had perinatal lethality, but we observed short snout and jaws, tongue protrusion, reduced NCC-derived cranial length, increased mineralization in nasal septum and hyoid bones, and less bone mineralization at interfrontal suture in mutants at E18.5. Importantly, the mutant nasal septum and turbinate cartilage histologically revealed gradual, premature accelerated hypertrophic differentiation. We then studied the underlying molecular mechanisms by performing RNA seq analysis and unexpectedly found that expression of Ihh and related signaling molecules was enhanced in mutant nasomaxillary tissues. To see if Pth1r and Ihh signaling are associated, we generated a Wnt1-Cre; Ihh fl / fl ; Pth1r fl / fl ; Tomato fl /+ (DKO) mouse and compared the phenotypes to those of each single knockout mouse: Wnt1-Cre; Ihh fl / fl ; Pth1r fl /+; Tomato fl /+ (Ihh-CKO) and Wnt1-Cre;Ihh fl /+; Pth1r fl / fl ; Tomato fl /+ (Pth1r-CKO). Ihh-CKO mice displayed a milder effect. Of note, the excessive hypertrophic conversion of the nasal cartilage framework observed in Pth1r-CKO was somewhat rescued DKO embryos. Further, a half cAMP responsive element and the 4 similar sequences containing 2 mismatches were identified from the promoter to the first intron in Ihh gene. Gli1-Cre ERT2 ; Pth1r fl / fl ; Tomato fl /+, a Pth1r-deficient model targeted in hedgehog responsive cells, demonstrated the enlarged hypertrophic layer and significantly more Tomato-positive chondrocytes accumulated in the nasal septum and ethmoidal endochondral ossification. Collectively, the data suggest a relevant Pth1r/Ihh interaction. Our findings obtained from novel mouse models for Pth1r signaling illuminate previously unknown aspects in craniofacial biology and development. [ABSTRACT FROM AUTHOR]